ID 5HT1D_HUMAN Reviewed; 377 AA.
AC P28221;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 27-MAR-2024, entry version 194.
DE RecName: Full=5-hydroxytryptamine receptor 1D;
DE Short=5-HT-1D;
DE Short=5-HT1D;
DE AltName: Full=Serotonin 1D alpha receptor;
DE Short=5-HT-1D-alpha;
DE AltName: Full=Serotonin receptor 1D;
GN Name=HTR1D; Synonyms=HTR1DA, HTRL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=1652050;
RA Hamblin M.W., Metcalf M.A.;
RT "Primary structure and functional characterization of a human 5-HT1D-type
RT serotonin receptor.";
RL Mol. Pharmacol. 40:143-148(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Placenta;
RX PubMed=1565658; DOI=10.1073/pnas.89.8.3630;
RA Weinshank R.L., Zgombick J.M., Macchi M.J., Branchek T.A., Hartig P.R.;
RT "Human serotonin 1D receptor is encoded by a subfamily of two distinct
RT genes: 5-HT1D alpha and 5-HT1D beta.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:3630-3634(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=1828434; DOI=10.1016/0014-4886(91)90142-y;
RA Gonzalez-Heydrich J., Peroutka S.J.;
RT "Postsynaptic localization of 5-HT1D receptor binding sites in human
RT caudate.";
RL Exp. Neurol. 113:28-30(1991).
RN [8]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=10452531; DOI=10.1016/s0014-5793(99)00918-7;
RA Xie Z., Lee S.P., O'Dowd B.F., George S.R.;
RT "Serotonin 5-HT1B and 5-HT1D receptors form homodimers when expressed alone
RT and heterodimers when co-expressed.";
RL FEBS Lett. 456:63-67(1999).
RN [9]
RP REVIEW.
RX PubMed=18476671; DOI=10.1021/cr078224o;
RA Nichols D.E., Nichols C.D.;
RT "Serotonin receptors.";
RL Chem. Rev. 108:1614-1641(2008).
RN [10]
RP REVIEW.
RX PubMed=20945968; DOI=10.33549/physiolres.931903;
RA Pytliak M., Vargova V., Mechirova V., Felsoci M.;
RT "Serotonin receptors - from molecular biology to clinical applications.";
RL Physiol. Res. 60:15-25(2011).
RN [11]
RP VARIANT LEU-265.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [12]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
CC -!- FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine
CC (serotonin). Also functions as a receptor for ergot alkaloid
CC derivatives, various anxiolytic and antidepressant drugs and other
CC psychoactive substances. Ligand binding causes a conformation change
CC that triggers signaling via guanine nucleotide-binding proteins (G
CC proteins) and modulates the activity of down-stream effectors, such as
CC adenylate cyclase. Signaling inhibits adenylate cyclase activity.
CC Regulates the release of 5-hydroxytryptamine in the brain, and thereby
CC affects neural activity. May also play a role in regulating the release
CC of other neurotransmitters. May play a role in vasoconstriction.
CC {ECO:0000269|PubMed:10452531, ECO:0000269|PubMed:1565658,
CC ECO:0000269|PubMed:1652050}.
CC -!- SUBUNIT: Homodimer. Heterodimer with HTR1B.
CC {ECO:0000269|PubMed:10452531}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10452531,
CC ECO:0000269|PubMed:1565658, ECO:0000269|PubMed:1652050}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:10452531,
CC ECO:0000269|PubMed:1565658, ECO:0000269|PubMed:1652050}.
CC -!- TISSUE SPECIFICITY: Detected in brain neocortex and caudate nucleus (at
CC protein level). {ECO:0000269|PubMed:1828434}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; M89955; AAA35491.1; -; Genomic_DNA.
DR EMBL; M81589; AAA60315.1; -; mRNA.
DR EMBL; AF498979; AAM21126.1; -; mRNA.
DR EMBL; BT007027; AAP35673.1; -; mRNA.
DR EMBL; AL049576; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007720; AAH07720.1; -; mRNA.
DR CCDS; CCDS231.1; -.
DR PIR; A53279; A53279.
DR RefSeq; NP_000855.1; NM_000864.4.
DR PDB; 7E32; EM; 2.90 A; R=2-377.
DR PDBsum; 7E32; -.
DR AlphaFoldDB; P28221; -.
DR SMR; P28221; -.
DR BioGRID; 109584; 3.
DR CORUM; P28221; -.
DR STRING; 9606.ENSP00000363748; -.
DR BindingDB; P28221; -.
DR ChEMBL; CHEMBL1983; -.
DR DrugBank; DB00918; Almotriptan.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB00714; Apomorphine.
DR DrugBank; DB01238; Aripiprazole.
DR DrugBank; DB14185; Aripiprazole lauroxil.
DR DrugBank; DB01200; Bromocriptine.
DR DrugBank; DB00248; Cabergoline.
DR DrugBank; DB01239; Chlorprothixene.
DR DrugBank; DB00363; Clozapine.
DR DrugBank; DB11273; Dihydroergocornine.
DR DrugBank; DB13345; Dihydroergocristine.
DR DrugBank; DB00320; Dihydroergotamine.
DR DrugBank; DB00216; Eletriptan.
DR DrugBank; DB01049; Ergoloid mesylate.
DR DrugBank; DB00696; Ergotamine.
DR DrugBank; DB00574; Fenfluramine.
DR DrugBank; DB00998; Frovatriptan.
DR DrugBank; DB12141; Gilteritinib.
DR DrugBank; DB01221; Ketamine.
DR DrugBank; DB12540; Lecozotan.
DR DrugBank; DB00589; Lisuride.
DR DrugBank; DB04948; Lofexidine.
DR DrugBank; DB00408; Loxapine.
DR DrugBank; DB00952; Naratriptan.
DR DrugBank; DB06096; NXN-188.
DR DrugBank; DB00334; Olanzapine.
DR DrugBank; DB00935; Oxymetazoline.
DR DrugBank; DB01267; Paliperidone.
DR DrugBank; DB00715; Paroxetine.
DR DrugBank; DB01186; Pergolide.
DR DrugBank; DB01224; Quetiapine.
DR DrugBank; DB00734; Risperidone.
DR DrugBank; DB00953; Rizatriptan.
DR DrugBank; DB09304; Setiptiline.
DR DrugBank; DB00669; Sumatriptan.
DR DrugBank; DB13025; Tiapride.
DR DrugBank; DB00726; Trimipramine.
DR DrugBank; DB01392; Yohimbine.
DR DrugBank; DB00246; Ziprasidone.
DR DrugBank; DB00315; Zolmitriptan.
DR DrugCentral; P28221; -.
DR GuidetoPHARMACOLOGY; 3; -.
DR GlyCosmos; P28221; 3 sites, No reported glycans.
DR GlyGen; P28221; 3 sites.
DR iPTMnet; P28221; -.
DR PhosphoSitePlus; P28221; -.
DR BioMuta; HTR1D; -.
DR DMDM; 112819; -.
DR PaxDb; 9606-ENSP00000363748; -.
DR Antibodypedia; 15559; 254 antibodies from 29 providers.
DR DNASU; 3352; -.
DR Ensembl; ENST00000374619.2; ENSP00000363748.1; ENSG00000179546.5.
DR GeneID; 3352; -.
DR KEGG; hsa:3352; -.
DR MANE-Select; ENST00000374619.2; ENSP00000363748.1; NM_000864.5; NP_000855.1.
DR UCSC; uc001bgn.3; human.
DR AGR; HGNC:5289; -.
DR CTD; 3352; -.
DR DisGeNET; 3352; -.
DR GeneCards; HTR1D; -.
DR HGNC; HGNC:5289; HTR1D.
DR HPA; ENSG00000179546; Group enriched (brain, intestine).
DR MIM; 182133; gene.
DR neXtProt; NX_P28221; -.
DR OpenTargets; ENSG00000179546; -.
DR PharmGKB; PA29550; -.
DR VEuPathDB; HostDB:ENSG00000179546; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000154484; -.
DR HOGENOM; CLU_009579_11_1_1; -.
DR InParanoid; P28221; -.
DR OMA; VWMISIS; -.
DR OrthoDB; 2999405at2759; -.
DR PhylomeDB; P28221; -.
DR TreeFam; TF316350; -.
DR PathwayCommons; P28221; -.
DR Reactome; R-HSA-390666; Serotonin receptors.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P28221; -.
DR SIGNOR; P28221; -.
DR BioGRID-ORCS; 3352; 8 hits in 1156 CRISPR screens.
DR GeneWiki; 5-HT1D_receptor; -.
DR GenomeRNAi; 3352; -.
DR Pharos; P28221; Tclin.
DR PRO; PR:P28221; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P28221; Protein.
DR Bgee; ENSG00000179546; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 57 other cell types or tissues.
DR Genevisible; P28221; HS.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IMP:UniProtKB.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007198; P:adenylate cyclase-inhibiting serotonin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; IBA:GO_Central.
DR GO; GO:0014827; P:intestine smooth muscle contraction; IMP:UniProtKB.
DR GO; GO:0050795; P:regulation of behavior; IEA:InterPro.
DR GO; GO:0040012; P:regulation of locomotion; IEA:InterPro.
DR GO; GO:0042310; P:vasoconstriction; IEA:InterPro.
DR CDD; cd15333; 7tmA_5-HT1B_1D; 1.
DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR InterPro; IPR000505; 5HT1D_rcpt.
DR InterPro; IPR002231; 5HT_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24248; ADRENERGIC RECEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR; 1.
DR PANTHER; PTHR24248:SF191; G-PROTEIN COUPLED RECEPTORS FAMILY 1 PROFILE DOMAIN-CONTAINING PROTEIN; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00514; 5HT1DRECEPTR.
DR PRINTS; PR01101; 5HTRECEPTOR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Membrane; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..377
FT /note="5-hydroxytryptamine receptor 1D"
FT /id="PRO_0000068927"
FT TOPO_DOM 1..38
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 39..64
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 65..75
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 76..98
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 99..112
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 113..134
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 135..154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 155..176
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 177..194
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 195..217
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 218..302
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 303..326
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 327..335
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 336..360
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 361..377
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 135..137
FT /note="DRY motif; important for ligand-induced conformation
FT changes"
FT /evidence="ECO:0000250"
FT MOTIF 352..356
FT /note="NPxxY motif; important for ligand-induced
FT conformation changes and signaling"
FT /evidence="ECO:0000250"
FT BINDING 118
FT /ligand="ergotamine"
FT /ligand_id="ChEBI:CHEBI:190463"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P28222"
FT BINDING 123
FT /ligand="ergotamine"
FT /ligand_id="ChEBI:CHEBI:190463"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P28222"
FT BINDING 190
FT /ligand="ergotamine"
FT /ligand_id="ChEBI:CHEBI:190463"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P28222"
FT CARBOHYD 5
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 17
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 21
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 111..188
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 265
FT /note="S -> L (in dbSNP:rs6299)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_011834"
FT HELIX 36..65
FT /evidence="ECO:0007829|PDB:7E32"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:7E32"
FT HELIX 72..90
FT /evidence="ECO:0007829|PDB:7E32"
FT HELIX 92..101
FT /evidence="ECO:0007829|PDB:7E32"
FT HELIX 107..141
FT /evidence="ECO:0007829|PDB:7E32"
FT HELIX 143..149
FT /evidence="ECO:0007829|PDB:7E32"
FT HELIX 152..170
FT /evidence="ECO:0007829|PDB:7E32"
FT HELIX 172..176
FT /evidence="ECO:0007829|PDB:7E32"
FT HELIX 195..205
FT /evidence="ECO:0007829|PDB:7E32"
FT HELIX 207..229
FT /evidence="ECO:0007829|PDB:7E32"
FT HELIX 285..326
FT /evidence="ECO:0007829|PDB:7E32"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:7E32"
FT HELIX 335..358
FT /evidence="ECO:0007829|PDB:7E32"
FT HELIX 361..370
FT /evidence="ECO:0007829|PDB:7E32"
SQ SEQUENCE 377 AA; 41907 MW; 0A4FCF81FFE2322A CRC64;
MSPLNQSAEG LPQEASNRSL NATETSEAWD PRTLQALKIS LAVVLSVITL ATVLSNAFVL
TTILLTRKLH TPANYLIGSL ATTDLLVSIL VMPISIAYTI THTWNFGQIL CDIWLSSDIT
CCTASILHLC VIALDRYWAI TDALEYSKRR TAGHAATMIA IVWAISICIS IPPLFWRQAK
AQEEMSDCLV NTSQISYTIY STCGAFYIPS VLLIILYGRI YRAARNRILN PPSLYGKRFT
TAHLITGSAG SSLCSLNSSL HEGHSHSAGS PLFFNHVKIK LADSALERKR ISAARERKAT
KILGIILGAF IICWLPFFVV SLVLPICRDS CWIHPALFDF FTWLGYLNSL INPIIYTVFN
EEFRQAFQKI VPFRKAS
//
